Long-term Safety of Vedolizumab for Inflammatory Bowel Disease in Children

Recruiting at 61 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Disqualifiers: Pregnancy, Heart failure, PML, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: Up to approximately 8 years

59 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the safety profile of long-term vedolizumab IV treatment in pediatric participants with UC or CD.

Will I have to stop taking my current medications?

You may continue taking certain medications like oral 5-aminosalicylic acid, corticosteroids, probiotics, antidiarrheals, specific antibiotics, azathioprine, 6-mercaptopurine, or methotrexate if you were already on them during a previous study. The trial does not specify stopping other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the drug Vedolizumab for treating inflammatory bowel disease in children?

Vedolizumab has been shown to be effective in treating moderate-to-severe ulcerative colitis and Crohn's disease in adults, with higher rates of clinical response and remission compared to a placebo. Although data in children is limited, its success in adults suggests potential benefits for pediatric use. ^{1 2 3 4 5}

Is vedolizumab safe for children with inflammatory bowel disease?

Vedolizumab, also known as Entyvio, has been studied for safety in children with inflammatory bowel disease, and while data is limited, it appears to be generally safe with a low risk of serious infections. More research is needed to fully understand its long-term safety in children. ^{2 3 4 6 7}

How is the drug vedolizumab different from other treatments for inflammatory bowel disease?

Vedolizumab is unique because it specifically targets the α4β7 integrin, which helps prevent immune cells from reaching the gut and causing inflammation, unlike other treatments that may suppress the immune system more broadly. ^{1 2 3 4 8}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for children and teens aged 2-17 with Ulcerative Colitis or Crohn's Disease who have previously responded to Vedolizumab treatment. They must be up-to-date on vaccinations, may use certain antibiotics, and can continue in the study after turning 18 if eligible. Pregnant or lactating females, those with serious health issues, or allergies to Vedolizumab cannot participate.

Inclusion Criteria

I completed Study MLN0002-2003 and met its success criteria.

I was between 2 to 17 years old when I joined the MLN0002-2003 study for UC or CD.

Participant's vaccinations are up to date as per inclusion criteria number 10 in MLN0002-2003

Exclusion Criteria

I am currently pregnant or breastfeeding.

I have symptoms that may suggest brain infection before starting the study drug.

I might need major surgery for my ulcerative colitis or Crohn's disease during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vedolizumab IV infusion every 8 weeks, with dose adjustments based on disease progression

Up to approximately 8 years

Every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving vedolizumab IV until it is commercially available or other drug access programs become available

Up to approximately 8 years

Treatment Details

Interventions

• Vedolizumab

Trial Overview The trial is testing the long-term safety of an IV medication called Vedolizumab in young patients with inflammatory bowel diseases like UC and CD. It aims to understand how safe it is when used over a longer period.

Participant Groups

Group I: Vedolizumab Low Dose Group Experimental Treatment 1 Intervention

Participants with UC or CD having baseline weight of \>= 30 kg will receive vedolizumab 150 mg and participants with UC or CD having baseline weight of \< 30 kg will receive vedolizumab 100 mg IV infusion, every 8 weeks until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available (whichever comes first), the participant turns 18 years of age and can be transitioned to commercial drug (up to approximately 8 years).

Group II: Vedolizumab High Dose Group Experimental Treatment 1 Intervention

Participants with UC or CD having baseline weight of greater than or equal to (\>=) 30 kilogram (kg) will receive vedolizumab 300 mg and participants with UC or CD having baseline weight of less than (\<) 30 kg will receive vedolizumab 200 mg, IV infusion, every 8 weeks until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available (whichever comes first), the participant turns 18 years of age and can be transitioned to commercial drug (up to approximately 8 years).

Vedolizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in United States as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Canada as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Japan as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Findings from Research

Vedolizumab is a humanized monoclonal antibody that targets the α4β7 integrin receptor, specifically designed for treating moderate-to-severe ulcerative colitis and Crohn's disease in adults who have not responded well to standard therapies.

It has received global approval, including in the US and EU, for patients who have had inadequate responses to other treatments, highlighting its role as an important option for those with difficult-to-treat inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: first global approval. Poole, RM.[2021]

Vedolizumab is an effective treatment for moderate-to-severe inflammatory bowel diseases like Crohn's disease and ulcerative colitis, with a well-established safety profile based on extensive clinical trial data and real-world studies.

The safety data indicates no unexpected long-term risks, making vedolizumab a strong candidate for combination therapies in patients with complex or refractory cases of inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. Honap, S., Netter, P., Danese, S., et al.[2023]

In patients treated with vedolizumab, the incidence of opportunistic infections was low, at 0.7 per 100 patient-years in clinical trials and 1.0 in long-term safety studies, indicating a favorable safety profile for this medication.

No cases of serious infections like progressive multifocal leukoencephalopathy or hepatitis B/C viral reactivation were reported, and most patients continued treatment without significant issues, suggesting vedolizumab is a safe option for managing inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. Ng, SC., Hilmi, IN., Blake, A., et al.[2023]

In phase III clinical trials, vedolizumab significantly improved clinical response and remission rates in patients with ulcerative colitis compared to placebo at both 6 and 52 weeks, demonstrating its efficacy for this condition.

While vedolizumab showed mixed results for Crohn's disease, it was effective in achieving clinical remission at 52 weeks in maintenance treatment, and it is generally well tolerated, with a lower risk of serious side effects compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. Garnock-Jones, KP.[2016]

Vedolizumab is a monoclonal antibody that effectively targets the α4β7 integrin to inhibit gut lymphocyte trafficking, providing a safe treatment option for patients with moderate to severe Crohn's disease and ulcerative colitis.

Unlike anti-TNF agents, which some patients may become intolerant to or lose response over time, vedolizumab offers a promising alternative for those who are primary nonresponders or have developed antidrug antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. Ha, C., Kornbluth, A.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Vedolizumab: first global approval. [2021]

2. England pubmed.ncbi.nlm.nih.gov

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vedolizumab for pediatrics with inflammatory bowel disease: a systematic review. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Vedolizumab: An Emerging Treatment Option for Pediatric Inflammatory Bowel Disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Vedolizumab Therapy in Severe Pediatric Inflammatory Bowel Disease. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. [2022]